Prevalidation of the Rat CFU-GM Assay for In Vitro Toxicology Applications
Prevalidation of the Rat CFU-GM Assay for In Vitro Toxicology Applications
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大鼠 CFU-GM 检测体外毒理学应用的预验证
DOI：
10.1177/026119291003800212
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
L. Gribaldo
中科院分区：
文献类型：
--
作者：
A. Pessina;A. Bonomi;L. Cavicchini;B. Albella;L. Cerrato;D. Parent;Y. Sibiril;R. Parchment;H. Behrsing;P. Verderio;S. Pizzamiglio;M. Giangreco;Carolina Baglio;V. Coccè;F. Sisto;L. Gribaldo
体外血液毒性试验被认为有可能显着减少和改进血液毒性试验中动物的使用。这些检测方法在所有类型的研究中均得到成功应用，但在临床前环境中的人体毒理学研究中并不常见，因为在这种情况下，监管检测不需要这些检测方法。此外，这些检测方法在弥合动物模型临床前毒理学研究和临床研究之间的差距方面发挥关键作用。在先前的研究中，已验证了殖民地形成单位-粒细胞巨噬细胞（CFU-GM）试验用于检测药物血液毒性（使用小鼠骨髓和人脐带血），并通过调整小鼠毒性的体内数据预测体内人最大耐受剂量（MTD）。最近，巨核细胞集落形成单位（CFU-MK）测定也已预先验证用于测试药物对巨核细胞的毒性。大鼠CFU-GM试验已被许多研究人员用于评估体外血液毒性的能力。虽然目前还没有，但数据比较的标准化程序可能非常重要，因为大鼠是毒物体内测试中使用最广泛的物种。本报告介绍了预验证研究的结果，该研究旨在分析该试验标准化操作程序的实验室内和实验室间变异性及其在体外测定药物对大鼠骨髓祖细胞的抑制浓度（IC）值的性能（CFU-GM）。结果表明，CFU-GM测定可以用冷冻保存的大鼠骨髓细胞（rBMC）进行。该测定代表了用于评价化合物的毒性的有用工具，在相对毒性（当比较不同分子时）和体内毒性程度的预测方面。使用该测定法可以大大减少实验程序中使用的大鼠数量，并且还可以有助于积累更多关于根据欧洲化学品注册、评估、授权和限制（REACH）计划建立的标准注册的化合物的毒性数据。
In vitro haematotoxicity assays are thought to have the potential to significantly reduce and refine the use of animals for haematotoxicity testing. These assays are used successfully in all types of studies — however, their use is not so common in human toxicology studies in the preclinical setting, as they are not required for regulatory testing in this case. Furthermore, these assays could play a key role in bridging the gap between preclinical toxicology studies in animal models and clinical investigations. In previous studies, the Colony Forming Unit-Granulocyte Macrophage (CFU-GM) assay has been validated for testing drug haematotoxicity (with both mouse bone-marrow and human cord blood) and for predicting the in vivo human maximal tolerated dose (MTD) by adjusting in vivo data on mouse toxicity. Recently, a Colony Forming Unit-Megakaryocyte (CFU-MK) assay has also been prevalidated for testing drug toxicity toward megakaryocytes. The rat CFU-GM assay has been used by many researchers for its ability to evaluate in vitro haematotoxicity. Although it is not yet available, a standardised procedure for data comparison could be very important, since the rat is the most widely-used species for the in vivo testing of toxicants. This report presents the results of the prevalidation study developed to analyse the intra-laboratory and inter-laboratory variability of a standardised operating procedure for this assay and its performance for the in vitro determination of the inhibitory concentration (IC) values of drugs on rat myeloid progenitors (CFU-GM). The results demonstrate that the CFU-GM assay can be performed with cryopreserved rat bone-marrow cells (rBMC). The assay represents a useful tool for evaluating the toxicity of a compound, in terms of both relative toxicity (when different molecules are compared) and the prediction of the degree of in vivo toxicity. The use of this assay could greatly reduce the number of rats used in experimental procedures, and could also contribute to the accumulation of more toxicity data on compounds to be registered according to the criteria established by the European Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) programme.
用于评估非致癌性血液毒性的替代测试系统。
影响因子：
10.4
作者：
Parchment,RE
通讯作者：
Parchment,RE